The utility of ultrasound imaging and therapy with microbubbles may be greatly enhanced by determining their impulse-response dynamics as a function of size and composition. Prior methods for microbubble characterization utilizing high-speed cameras, acoustic transducers and laser-based techniques typically scan a limited frequency range. Here, we report on the use of a novel photoacoustic technique to measure the impulse response of single microbubbles. Individual microbubbles are driven with a broadband photoacoustic wave generated by a nanosecond-pulse laser illuminating an optical absorber. The resulting microbubble oscillations were detected by following transmission of a second laser as it passes twice through the microbubble. The system could even resolve oscillations resulting from a single-shot. As a proof-of-concept study, the size-dependent, linear impulse response of lipid-coated microbubbles was characterized using this technique. This unique method of microbubble characterization with exceptional spatiotemporal resolution opens new avenues for capturing and analyzing microbubble system dynamics.

The interaction between an acoustically driven microbubble and a surface is of interest for a variety of applications, such as ultrasound imaging therapy. Prior investigations have mainly focused on acoustic effects of a rigid boundary, where it was generally observed that the wall increases inertia and reduces the microbubble resonance frequency. Here we investigate the response of a lipid-coated microbubble adherent to a rigid wall. Firm adhesion between the microbubble and a glass surface was achieved through either specific (biotin/avidin) or nonspecific (lipid/glass) interactions. Total internal reflection fluorescence microscopy was used to verify conditions leading to either adhesion or non-adhesion of the bubble to a glass or rigid polymer surface. Individual microbubbles were driven acoustically to sub-nanometer-scale radial oscillations using a photoacoustic technique. Remarkably, adherent microbubbles were shown to have a higher resonance frequency than non-adherent microbubbles resting against the wall. Analysis of the resonance curves indicates that adhesion stiffens the bubble by an apparent increase in the shell elasticity term and decrease in the shell viscosity. Based on these results, we conclude that surface adhesion is dominant over acoustic effects for low-amplitude microbubble oscillations.

We show here that adhesion to a solid substrate increases the resonance frequency of a lipid-coated microbubble by causing an apparent increase in shell stiffness. Using our previously developed photoacoustic measurement technique to drive individual microbubbles into small-amplitude oscillations, we found that biotinylated microbubbles adherent to a streptavidin-coated glass coverslip had much higher resonance frequencies than unbound microbubbles. The frequency responses of the bound microbubbles agree well with a linearized form of the modified Rayleigh-Plesset model with an added increase of shell elasticity. The apparent shell elasticity increased from 0.5 N/m for unbound microbubbles to 2.6 N/m. These findings may be used to better understand microbubble dynamics for applications in ultrasound imaging and therapy.